title: The cerebrospinal fluid provides a proliferative niche for neural progenitor cells.
abstract: Cortical development depends on the active integration of cell-autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the cerebrospinal fluid (CSF), which contacts this apical domain, has an age-dependent effect on proliferation, much of which is attributable to Igf2, but that CSF contains other signaling activities as well. CSF samples from patients with glioblastoma multiforme show elevated Igf2 and stimulate stem cell proliferation in an Igf2-dependent manner. Together, our findings demonstrate that the apical complex couples intrinsic and extrinsic signaling, enabling progenitors to sense and respond appropriately to diffusible CSF-borne signals distributed widely throughout the brain. The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions.
authors.affiliation: Division of Genetics, Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA 02115, USA.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Lehtinen
authors.forename: Mauro W
authors.initials: MW
authors.lastname: Zappaterra
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Yawei J
authors.initials: YJ
authors.lastname: Yang
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Hill
authors.forename: Melody
authors.initials: M
authors.lastname: Lun
authors.forename: Thomas
authors.initials: T
authors.lastname: Maynard
authors.forename: Dilenny
authors.initials: D
authors.lastname: Gonzalez
authors.forename: Seonhee
authors.initials: S
authors.lastname: Kim
authors.forename: Ping
authors.initials: P
authors.lastname: Ye
authors.forename: A Joseph
authors.initials: AJ
authors.lastname: D'Ercole
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wong
authors.forename: Anthony S
authors.initials: AS
authors.lastname: LaMantia
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Walsh
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001932:Brain Neoplasms / Q000134:cerebrospinal fluid; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D002555:Cerebrospinal Fluid / Q000502:physiology*; D005909:Glioblastoma / Q000134:cerebrospinal fluid; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D008565:Membrane Proteins; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D009703:Nucleoside-Phosphate Kinase; C499979:Mpp5 protein, mouse; D051059:PTEN Phosphohydrolase